A small population of vasculitogenic T cells expands and has skewed T cell receptor usage after culture with syngeneic smooth muscle cells
Autor: | Matyas Sandor, Dana C. Baiu, Zsuzsa Fabry, Michael N. Hart, Brad J Swanson |
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Rok vydání: | 2003 |
Předmět: |
CD4-Positive T-Lymphocytes
Vasculitis Receptors Antigen T-Cell alpha-beta Myocytes Smooth Muscle Immunology Biology Muscle Smooth Vascular Autoimmune Diseases Mice Interleukin 21 Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell Interleukin 3 Mice Inbred BALB C CD40 Natural killer T cell Adoptive Transfer Complementarity Determining Regions Molecular biology Coculture Techniques Disease Models Animal Interleukin 12 biology.protein Cell Division |
Zdroj: | Journal of Autoimmunity. 20:125-133 |
ISSN: | 0896-8411 |
DOI: | 10.1016/s0896-8411(02)00113-0 |
Popis: | Adoptive transfer of lymphocytes co-cultured with syngeneic smooth muscle (SM) cells to healthy recipient mice results in vasculitic lesions predominantly in post-capillary venules. The present study focuses on the mechanisms by which the disease-inducing CD4(+) T cells are generated in co-culture of lymphocytes with SM cells. Microvascular SM cells provide survival signals to both CD4(+) and CD8(+) naïve syngeneic T cells and can activate only a limited range of CD4(+) T lymphocytes in culture. Additionally, approximately 0.4% of the original CD4(+) T cells divide at least twice in co-culture with SM cells. Survival of CD4(+) T cells in co-culture is dependent on a TCR mediated process, since transgenic CD4 (+)cells with a unique specificity for a non-murine peptide do not survive in culture with SM. Analysis of TCR Vbeta shows no superantigen activation of T cells following co-culture with SM cells. Spectratype analysis of TCR Vbeta Jbeta segment usage reveals a skewage in the TCR repertoire of T cells co-cultured with SM, and also of T cells from vasculitic lung. These results are consistent with a specific immune response of pathogenic T cells against one or more activating antigenic determinants of the microvascular SM cells, in contrast to non-specific cytokine activation. |
Databáze: | OpenAIRE |
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